Histone H3 lysine 4 dimethylation is enriched on the inactive sex chromosomes in male meiosis but absent on the inactive X in female somatic cells

Abstract

Inactivation of the X chromosome occurs in female somatic cells and in male meiosis. In both cases, the inactive X chromosome undergoes changes in histone modifications including deacetylation of core histone proteins and enrichment with histone H3 lysine 9 (H3-K9) dimethylation. In this study we show that while the inactive X in female somatic cells is largely devoid of H3-K4 dimethylation, the inactive X in male meiosis is enriched with this modification. However, the inactive X chromosome in female somatic cells and the inactive X and Y in male meiosis are devoid of H3-K4 trimethylation. Further, trimethylation of H3-K4 is present at discrete regions along most of the autosomes, while H3-K4 dimethylation shows a more homogenous staining. Also, the Y chromosome is largely devoid of H3-K4 di- and trimethylation in somatic cells of both humans and mice, however, the Y chromosome is enriched with H3-K4 di- but not trimethylation throughout spermatogenesis. Our results provide insights into the differences between female somatic cells and male germ cells in inactivating the X chromosome, and suggest that trimethylation, and not dimethylation, of H3-K4 is a more robust indicator of the active regions of the genome.

Trimethylation of Histone H3 Lysine 4 is an Epigenetic Mark at Regions Escaping Mammalian X Inactivation

“…21,31 However, as expected the X and Y chromosomes become enriched with the repressive modification H3K9me2 from the late pachytene stage to the early spermatid stage. 21 Analysis of the male X and Y during spermatogenesis using an antibody for RNA polymerase II (H5) when phosphorylated at serine 2 suggest that there are several regions that escape XY inactivation (XYi), which begins at the pachytene stage of meiosis.…”

Increased phosphorylation and dimethylation of XY body histones in theHr6b-knockout mouse is associated with derepression of the X chromosome

“…Somehow, lack of HR6B affects H2A T120ph , and this may subsequently lead to increased H3 K4m1 and H3 K4m2 , specifically in the XY body. Previously, Khalil and Driscoll (Khalil and Driscoll, 2006), reported that H3 K4m2 is upregulated on the silent XY body of wild-type diplotene spermatocytes. Our data confirm their findings, and we show that in Hr6b-knockout spermatocytes this modification is further upregulated on X and Y.…”

Increased sex chromosome expression and epigenetic abnormalities in spermatids from male mice with Y chromosome deletions

“…However, the X and Y chromosomes are continually remodelled during the transition between meiosis and spermiogenesis, and histone modifications associated with transcriptionally active chromatin [e.g. histone acetylation and histone H3 dimethylated on lysine 4 (H3K4me2)] are also enriched on PMSC in round spermatids (Baarends et al, 2007;Greaves et al, 2006;Khalil and Driscoll, 2006). These epigenetic changes could explain why XY spermatid silencing is less complete than MSCI, and might reflect a need to retain expression of some X-and Yencoded genes that are essential for spermiogenesis.…”